In vitro and In vivo efficacy of an LpxC inhibitor, CHIR-090, alone or combined with colistin against Pseudomonas aeruginosa biofilm
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In vitro and In vivo efficacy of an LpxC inhibitor, CHIR-090, alone or combined with colistin against Pseudomonas aeruginosa biofilm. / Tan, Jun Hou; Vidaillac, Celine; Yam, Joey Kuok Hoong; Chua, Song Lin; Givskov, Michael; Yang, Liang.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 7, e02223-16, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - In vitro and In vivo efficacy of an LpxC inhibitor, CHIR-090, alone or combined with colistin against Pseudomonas aeruginosa biofilm
AU - Tan, Jun Hou
AU - Vidaillac, Celine
AU - Yam, Joey Kuok Hoong
AU - Chua, Song Lin
AU - Givskov, Michael
AU - Yang, Liang
PY - 2017
Y1 - 2017
N2 - With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined with CHIR-090, a potent LpxC inhibitor, against in vitro and in vivo Pseudomonas aeruginosa biofilms. Four P. aeruginosa isolates with various colistin susceptibilities were chosen for evaluation. The tested isolates of P. aeruginosa exhibited MIC values ranging from 1 to 64 and 0.0625 to 0.5 μg/ml for colistin and CHIR-090, respectively. Against 24-h static biofilms, minimum biofilm eradication concentration values ranged from 256 to 512 and 8 to >128 μg/ml for colistin and CHIR-090, respectively. Interestingly, subinhibitory concentrations of CHIR-090 contributed to the eradication of subpopulations of P. aeruginosa with the highest colistin MIC values. The combination of colistin and CHIR-090 at subinhibitory concentrations demonstrated synergistic activity both in vivo and in vitro and prevented the formation of colistin-tolerant subpopulations in in vitro biofilms. In summary, our study highlights the in vivo and in vitro synergistic activity of the colistin and CHIR-090 combination against both colistin-susceptible and -nonsusceptible P. aeruginosa biofilms. Further studies are warranted to investigate the clinical relevance of the combination of these two antimicrobials and outline the underlying mechanism for their synergistic action.
AB - With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined with CHIR-090, a potent LpxC inhibitor, against in vitro and in vivo Pseudomonas aeruginosa biofilms. Four P. aeruginosa isolates with various colistin susceptibilities were chosen for evaluation. The tested isolates of P. aeruginosa exhibited MIC values ranging from 1 to 64 and 0.0625 to 0.5 μg/ml for colistin and CHIR-090, respectively. Against 24-h static biofilms, minimum biofilm eradication concentration values ranged from 256 to 512 and 8 to >128 μg/ml for colistin and CHIR-090, respectively. Interestingly, subinhibitory concentrations of CHIR-090 contributed to the eradication of subpopulations of P. aeruginosa with the highest colistin MIC values. The combination of colistin and CHIR-090 at subinhibitory concentrations demonstrated synergistic activity both in vivo and in vitro and prevented the formation of colistin-tolerant subpopulations in in vitro biofilms. In summary, our study highlights the in vivo and in vitro synergistic activity of the colistin and CHIR-090 combination against both colistin-susceptible and -nonsusceptible P. aeruginosa biofilms. Further studies are warranted to investigate the clinical relevance of the combination of these two antimicrobials and outline the underlying mechanism for their synergistic action.
KW - Biofilms
KW - Colistin
KW - LpxC inhibitor
KW - Pseudomonas aeruginosa
U2 - 10.1128/AAC.02223-16
DO - 10.1128/AAC.02223-16
M3 - Journal article
C2 - 28461320
AN - SCOPUS:85021663924
VL - 61
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 7
M1 - e02223-16
ER -
ID: 182423348